Source: Naturally derived CNS stimulant extracted
and refined from the leaves of the coca plant (Erythroxylon coca),
grown primarily in the Andean region of South America and to a lesser
extent in India, Africa and Indonesia. The picked coca leaves are dried
in the open air and then “stomped” as part of the process
to extract the alkaloid, resulting in coca paste and eventually cocaine
hydrochloride. It is illegal to possess and sell cocaine in the U.S.
and cocaine is a Schedule II controlled substance. “Crack” is
the street name given to cocaine that has been processed from cocaine
hydrochloride. It is prepared by adding baking soda to aqueous cocaine
hydrochloride and heating it until the free-base cocaine precipitates
into small pellets. The mixture is cooled and filtered, and then the “rocks” are
smoked in a crack pipe.

Drug Class: CNS stimulant, local anesthetic.

Medical and Recreational Uses: Minor use as
a topical local anesthetic for ear, nose and throat surgery. Traditionally,
the coca leaves are chewed or brewed into a tea for refreshment and to
relieve fatigue. Recreationally, cocaine is u sed to increase alertness,
relieve fatigue, feel stronger and more decisive, and is abused for its
intense euphoric effects.

Potency, Purity and Dose: In ear, nose and
throat surgery cocaine is commercially supplied as the hydrochloride
salt in a 40 or 100 mg/mL solution. Depending on the demographic region,
street purity of cocaine hydrochloride can range from 20-95%, while that
of crack cocaine is 20-80%. The hydrochloride powder is often diluted
with a variety of substances such as sugars for bulk (lactose, sucrose,
inositol, mannitol), other CNS stimulants (caffeine, ephedrine, phenylpropanolamine),
or other local anesthetics (lidocaine, procaine, benzocaine). Commonly
abused doses are 10-120 mg. Repeated doses are frequently taken to avoid
the dysphoric crash that often follows the initial intense euphoric effects.
Cocaine is frequently used in combination with other drugs; injected
with heroin (“speedball”) or taken with alcohol to reduce
irritability; smoked with phencyclidine (“tick”); and smoked
in marijuana blunts (“turbo”).

Route of Administration: Topically applied
for use as a local anesthetic. Recreationally, coca leaves can be chewed,
however, cocaine abusers typically smoke “crack” in a glass
pipe or inject the hydrochloride salt intravenously. Cocaine hydrochloride
can be smoked to some effect but this is very inefficient as the powder
tends to burn rather than vaporize. Snorting (insufflation/intranasal)
is also popular. Subcutaneous injection (skin-popping) is rarely used.

Pharmacodynamics: Cocaine is a strong CNS
stimulant that interferes with the reabsorption process of catecholamines,
particularly dopamine, a chemical messenger associated with pleasure
and movement. Cocaine prevents the reuptake of dopamine by blocking the
dopamine transporter which leads to increased extracellular dopamine,
resulting in chronic stimulation of postsynaptic dopamine receptors.
This results in the euphoric ‘rush’. When dopamine levels
subsequently fall, users experience a dysphoric ‘crash’.
Similarly, cocaine interferes with the uptake of norepinephrine and serotonin
(5-HT), leading to accumulation of these neurotransmitters at postsynaptic
receptors. As a local anesthetic, cocaine reversibly blocks the initiation
and conduction of the nerve impulse. Cocaine additionally produces vasoconstriction
and dilated pupils.

Pharmacokinetics: Cocaine is rapidly absorbed
following smoking, snorting and intravenous administration. Bioavailability
is 57% following snorting and ~70% following smoking. Cocaine is 91%
bound in plasma. Cocaine is extensively metabolized to a variety of compounds:
benzoylecgonine, ecgonine, and ecgonine methyl ester are the major metabolites
and are centrally inactive. Benzoylecgonine is produced upon loss of
the methyl group and is the major urinary metabolite. Norcocaine is a
very minor metabolite, but is active and neurotoxic. Cocaethylene, formed
following concurrent ingestion of cocaine and alcohol, is also active
and is equipotent to cocaine in blocking dopamine reuptake. The apparent
half-life for cocaine is short, approximately 0.8 ± 0.2 hours,
while the half-life of benzoylecgonine is 6 hours.

Molecular Interactions / Receptor Chemistry: The
cytochrome P450 3A4 isoenzyme is responsible for the N-demethylation
of cocaine to norcocaine. Potential inhibitors of the 3A4 isoenzyme could
decrease the rate of drug elimination if administered concurrently, while
potential inducers could increase the rate of drug elimination. Cocaine
itself is an inhibitor of the CYP2D6 isoform.

Blood to Plasma Concentration Ratio: averages
~ 1.0

Interpretation of Blood Concentrations: The
presence of cocaine at a given blood concentration cannot usually be
associated with a degree of impairment or a specific effect for a given
individual without additional information. This is due to many factors,
including individual levels of tolerance to the drug and artifactual
changes in cocaine concentrations on storage. There is a large overlap
between therapeutic, toxic and lethal cocaine concentrations and adverse
reactions have been reported after prolonged use even with no measurable
parent drug in the blood. Typical concentrations in abuse range from
0-1mg/L, however, concentrations up to 5mg/L and higher are survivable
in tolerant individuals. After single doses of cocaine, plasma concentration
typically average 0.2-0.4 mg/L. Repeated doses of cocaine may result
in concentrations greater than 0.75 mg/L.

Interpretation of Urine Test Results: Urinary
excretion is less than 2% for unchanged cocaine, 26-39% for benzoylecgonine,
and 18-22% for ecgonine methyl ester. 64-69% of the initial dose is recovered
after 3 days. Very low concentrations of cocaine may be detected in urine
during the initial few hours, however, benzoylecgonine persists in urine
at detectable concentrations from 2-4 days. Chronic, heavy use of cocaine
can result in detectable amounts of benzoylecgonine in urine for up to
10 days following a binge.

Burnt lips and fingers from crack pipes are frequently seen, as are
rashes and skin reddening from scratching. Smokers may suffer from acute
respiratory problems including cough, shortness of breath, and severe
chest pains with lung trauma and bleeding. Prolonged cocaine snorting
can result in ulceration of the mucous membrane of the nose. The injecting
drug user is at risk for transmitting or acquiring HIV infection/AIDS
if needles or other injection equipment are shared.

Duration of Effects: The faster the absorption
the more intense and rapid the high, but the shorter the duration of
action. Injecting cocaine produces an effect within 15-30 seconds. A
hit of smoked crack produces an almost immediate intense experience and
will typically produce effects lasting 5-15 minutes. Similarly, snorting
cocaine produces effects almost immediately and the resulting high may
last 15-30 minutes. The effects onset more slowly after oral ingestion
(~1 hour). General effects will persist for 1-2 hours depending on the
dose and late phase effects following binge use may last several days.

Tolerance, Dependence and Withdrawal Effects: Cocaine
is a powerfully addictive drug of abuse and an appreciable initial tolerance
to the euphoric high may develop. Cocaine is psychologically addicting,
particularly with heavy or frequent use, and possibly physically addicting
as well. The short duration of effects is one reason leading to probability
of addition. As effects wear off, more drug is frequently administered
and a pattern of repeated use occurs. Following binge use of cocaine,
the “crash” can last from 9 hours to 4 days and may consist
of agitation, depressed moods, insomnia to hypersomnolence, and initial
drug craving. Withdrawal symptoms can typically last from 1-3 weeks and
may consist of alternating low and high drug craving, low to high anxiety,
paranoia, dysphoria, depression, apathy, irritability, disorientation,
hunger, fatigue, bradycardia, and long periods of sleep.

Drug Interactions: The combined use of cocaine
and ethanol forms cocaethylene in the body, a substance which intensifies
cocaine’s euphoric effects while possibly increasing the risk of
sudden death. In laboratory studies, cocaine has been shown to partially
reverse some of the adverse effects of alcohol, but may contribute to
the detrimental effects of marijuana.

Performance Effects: Most laboratory-based
studies have been limited by the low doses of cocaine that were allowed.
At these single low doses, studies have shown performance enhancement
in attentional abilities and increased behavioral and cortical arousal,
but have no enhancement of effects on learning, memory, and other cognitive
processes. Faster reaction times and diminished effects of fatigue have
been observed. Improvements were greatest in behaviorally impaired subjects
(e.g. sleep deprived, fatigued, or concurrent use of ethanol) and least
improvements were observed in well-rested, healthy subjects. More deleterious
effects are expected after higher doses, chronic ingestion and during
drug withdrawal, and include agitation, anxiety, distress, inability
to focus on divided attention tasks, inability to follow directions,
confusion, hostility, time distortion, and poor balance and coordination.
Laboratory studies have also demonstrated increased risk taking (rapid
braking or steering) and deleterious effects on vision related to mydriasis.
Self-reported increases in sensitivity to light, seeing halos around
bright objects, flashes or movement of light in peripheral field, difficulty
focusing, blurred vision, and glare recovery problems have been reported.

Effects on Driving: Observed signs of impairment
in driving performance have included subjects speeding, losing control
of their vehicle, causing collisions, turning in front of other vehicles,
high-risk behavior, inattentive driving, and poor impulse control. As
the effects of cocaine wear off subjects may suffer from fatigue, depression,
sleepiness, and inattention. In epidemiology studies of driving under
the influence cases, accidents, and fatally injured drivers, between
8-23% of subjects have had cocaine and/or metabolites detected in their
blood. An examination of 253 fatally injured drivers in Wayne County,
Michigan between 1996-1998, found that 10% of cases were positive for
blood cocaine and/or metabolites. On review of accident and witness reports,
aggressive driving (high speed and loss of vehicle control) was revealed
as the most common finding. Ethanol was detected in 56% of these cases,
and all of these drivers lost control of their vehicles. In Memphis,
Tennessee in 1993, 13% of 150 drivers stopped for reckless driving were
determined to be driving under the influence of cocaine based on observations
of behavior and appearance, performance on field sobriety tests, and
positive urine cocaine tests.

A 25 year-old male driver, who made an improper turn against oncoming
traffic, had a blood cocaine concentration of 0.04 mg/L and 0.06 mg/L
of benzoylecgonine, 2 hours after the collision. A 30 year-old female
caused an accident after failing to stop at a traffic light; the driver
admitted to ingesting a large amount of cocaine ~ 2.5 hours prior to
the collision, and 0.32 mg/L cocaine was detected in her blood 1 hour
post accident.

Panel’s Assessment of Driving Risks: Single
low doses of cocaine may improve mental and motor performance in persons
who are fatigued or sleep deprived, however, cocaine does not necessarily
enhance the performance of otherwise normal individuals. Cocaine may
enhance performance of simple tasks but not complex, divided-attention
tasks such as driving. Most laboratory studies have been limited by the
low single doses of cocaine administered to subjects. At these low doses,
most studies showed performance enhancement in attentional abilities
but no effect on cognitive abilities. Significant deleterious effects
are expected after higher doses, chronic ingestion, and during the crash
or withdrawal phase.